Self‐assembled adult adipose‐derived stem cell spheroids combined with biomaterials promote wound healing in a rat skin repair model

Abstract

Adult adipose-derived stem cells (ASCs) are a type of multipotent mesenchymal stem cells (MSCs) with easy availability and serve as a potential cell source for cell-based therapy. Three-dimensional MSC spheroids may be derived from the self-assembly of individual MSCs grown on certain polymer membranes. In this study, we demonstrated that the self-assembled ASC spheroids on chitosan-hyaluronan membranes expressed more cytokine genes (fibroblast growth factor 1, vascular endothelial growth factor, and chemokine [C-C motif] ligand 2) as well as migration-associated genes (chemokine [C-X-C motif] receptor type 4 and matrix metalloprotease 1) compared with ASC dispersed single cells grown on culture dish. To evaluate the in vivo effects of these spheroids, we applied ASC single cells and ASC spheroids in a designed rat skin repair model. Wounds of 15 × 15 mm were created on rat dorsal skin, where ASCs were administered and covered with hyaluronan gel/chitosan sponge to maintain a moist environment. Results showed that skin wounds treated with ASC spheroids had faster wound closure and a significantly higher ratio of angiogenesis. Tracking of fluorescently labeled ASCs showed close localization of ASC spheroids to microvessels, suggesting enhanced angiogenesis through paracrine effects. Based on the in vitro and in vivo results, the self-assembled ASC spheroids may be a promising cellular source for skin tissue engineering and wound regeneration.

Effects of electrospun scaffolds of di-O-butyrylchitin and poly-(ε-caprolactone) on wound healing

“…Enhanced angiogenesis and accelerated wound healing has also been observed after implantation of chitosanhyaluronan membranes with adipose-derived stem cells to the wound in the rat. 37 Our main findings were focused on characterization of the processing techniques and structure and on describing the biological effects of biodegradable polymers. However, previous papers have examined only the classical forms, such as fibres, nonwovens, knitting products, foams or films.…”

Mesenchymal stem cells: potential for therapy and treatment of chronic non-healing skin wounds

“…127 Very recent evidence coming from animal models suggest that also allogenic ADSC sheets, 128 or ADSC spheroids assembled on polymer membranes could be a future therapeutic approach. 129 The advantage of such bioengineering techniques is to provide ADSCs with a more favorable milieu for cytokine and chemokine production, as demonstrated by animal models. 129 Furthermore, the use of antibacterial materials such as chitosan may reduce the risk of bacterial growth, thus reducing the incidence of side effect.…”

Biomaterials for Tendon/Ligament and Skin Regeneration

“…Chitosan-hyaluron membrane: Hsu et al investigated adult ADSCs spheroids combined with a chitosan-hyaluron membrane and showed biomaterial combined with stem cells promoted wound healing in a rat skin repair model [32]. Dense and porous chitosan-xanthan membranes seeded with multipotent mesenchymal stromal cells were evaluated for the treatment of skin wounds.…”